Advanced Rare TumoursPhase 2NCT02879162
Durvalumab and Tremelimumab in Patients With Advanced Rare Tumours
A Phase 2 study testing Durvalumab and Tremelimumab in people with Advanced Rare Tumours, run by Canadian Cancer Trials Group at 13 sites in Canada.
Trial summary
The standard or usual treatment for this disease may be chemotherapy or other types of treatment to slow the spread of the disease and relieve some symptoms of this cancer. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Advanced Rare Tumours
- What is being tested?
- Durvalumab and Tremelimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 13 sitesCanada
- Study dates
- 14 Dec 2016to 29 Jan 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must have histologically and/or cytologically confirmed cancer that is advanced / metastatic / recurrent or unresectable and for which no curative therapy exists as follows:
- Salivary carcinoma (excluding adenoid cystic carcinoma histology)
- Carcinoma of unknown primary with tumour infiltrating lymphocytes (TILs) and/or expressing PD-L1
- Mucosal melanoma
- Acral melanoma
- Osteosarcoma
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- Undifferentiated pleomorphic sarcoma
- Clear cell carcinoma of the ovary
- Squamous cell carcinoma of the anal canal (SCCA)
- All patients must have a tumour tissue from their primary or metastatic tumour available
- Presence of clinically and/or radiologically documented disease. All radiology studies must be performed within 28 days prior to registration (within 35 days if negative).
- All patients must have at least one measurable lesion as defined by RECIST 1.1 that has not been the site of the protocol mandated biopsy. The criteria for defining measurable disease are as follows:
- CT scan (with slice thickness of 5 mm) ≥ 10 mm --> longest diameter Lymph nodes by CT scan ≥ 15 mm --> measured in short axis
- Patients must be ≥ 16 years of age.
- Patients must have an ECOG performance status of 0 or 1.
- Previous Therapy
- Cytotoxic Chemotherapy:
- Patients may have received prior chemotherapy - no limit on number of prior regimens.
- Other Systemic Therapy:
- Patients may have received other prior therapies including, angiogenesis inhibitors, PARP inhibitors or signal transduction inhibitors (tyrosine kinase inhibitors). Prior therapy with PD-1/PD-L1 or CTLA-4 inhibitors is not allowed.
- Patients must have recovered from all reversible toxicity related to prior chemotherapy or systemic therapy (unless grade 1, irreversible, or considered by investigator as not clinically significant) and have adequate washout as follows:
- Longest of one of the following:
- Two weeks
- 5 half-lives for investigational agents
- Standard cycle length of standard therapies
- Radiation:
- Prior external beam radiation is permitted provided a minimum of 28 days (4 weeks) have elapsed between the last dose of radiation and date of registration. Exceptions may be made for low-dose, non-myelosuppressive radiotherapy after consultation with CCTG senior investigator. Concurrent radiotherapy is not permitted. Patients planned for concurrent chemotherapy-radiation are not eligible.
- Surgery:
- Previous surgery is permitted provided that a minimum of 28 days (4 weeks) have elapsed between any major surgery and date of registration, and that wound healing has occurred.
- Lab Requirements:
- Absolute neutrophils ≥ 1.5 x 10^9/L Platelets ≥ 100 x 10^9/L Hemoglobin ≥ 90 g/L Bilirubin ≤ 1.5 x ULN (upper limit of normal) AST and ALT ≤ 2.5 x ULN (if liver metastases are present, ≤ 5 x ULN) Serum creatinine < 1.25 x ULN or: Creatinine clearance ≥ 40 mLs/min
- Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements
- Women/men of childbearing potential must have agreed to use a highly effective contraceptive method.
- Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre.
- Subjects should not donate blood while participating in this study, or for at least 90 days following the last infusion of durvalumab or tremelimumab.
- In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient registration
Who cannot join
- Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other cancers curatively treated with no evidence of disease for ≥ 5 years.
- Active or prior documented autoimmune or inflammatory disorders including inflammatory bowel disease (e.g. colitis or Crohn's disease), diverticulitis with the exception of diverticulosis, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), rheumatoid arthritis, hypophysitis, uveitis, etc., within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
- Patients with alopecia.
- Patients with Grave's disease, vitiligo or psoriasis not requiring systemic treatment (within the last 2 years).
- Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement.
- History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of registration.
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- Live attenuated vaccination administered within 30 days prior to registration.
- History of hypersensitivity to durvalumab or tremelimumab or any excipient. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab.
- Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous year or cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects). Patients with a significant cardiac history, even if controlled, should have a LVEF ≥ 50%.
- Untreated symptomatic brain metastases or brain metastases in whom radiation or surgery is indicated.
- Concurrent treatment with other investigational drugs or anti-cancer therapy.
- Patients with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol (incl corticosteroid administration), or would put the patient at risk. This includes but is not limited to:
- History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements.
- Active infection requiring systemic therapy; (including any patient known to have active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) or tuberculosis or any infection requiring systemic therapy).
- Active peptic ulcer disease or gastritis.
- Known pneumonitis or pulmonary fibrosis with clinically significant impairment of pulmonary function.
- Pregnant or lactating women.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
Canada13 sites
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
QEII Health Sciences Centre
Halifax, Nova Scotia, B3H 1V7
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, L8V 5C2
BCCA - Cancer Centre for the Southern Interior
Kelowna, British Columbia, V1Y 5L3
London Regional Cancer Program
London, Ontario, N6A 5W9
CHUM-Centre Hospitalier de l'Universite de Montreal
Montreal, Quebec, H2X 3E4
The Research Institute of the McGill University
Montreal, Quebec, H4A 3J1
Ottawa Hospital Research Institute
Ottawa, Ontario, K1H 8L6
Allan Blair Cancer Centre
Regina, Saskatchewan, S4T 7T1
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, S7N 4H4
University Health Network
Toronto, Ontario, M5G 2M9
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, V5Z 4E6
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
About this study
Official title: A Phase II Study of Durvalumab and Tremelimumab in Patients With Advanced Rare Tumours
The standard or usual treatment for this disease may be chemotherapy or other types of treatment to slow the spread of the disease and relieve some symptoms of this cancer.
Read the detailed description
Durvalumab is a new type of drug for many types of cancer. Laboratory tests show that it works by allowing the immune system to detect cancer and stimulate the immune response. This may help to slow down the growth of cancer or may cause cancer cells to die. Durvalumab has been shown to shrink tumours in animals and has been studied in 5000 people and seems promising but it is not clear if it can offer better results than standard treatment alone.
Tremelimumab is a new type of drug for various types of cancers. It works in a similar way to durvalumab and may improve the effect of durvalumab. This may also help slow the growth of the cancer cells or may cause cancer cells to die. Tremelimumab has been shown to shrink tumours in animals and has been studied in 1500 people and seems promising but it is not clear if it can offer better results than standard treatment alone when used with durvalumab
Combinations of durvalumab and tremelimumab have also been studied and when combined have been shown to increase tumour shrinkage in animals compared to either drug alone. While the combination has been studied in 250 people, it is not clear if it can offer better results than standard treatment.
- Conditions
- Advanced Rare Tumours
- Being tested
- Durvalumab, Tremelimumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
TremelimumabDrug
| Study group | Role | What they receive |
|---|---|---|
| Durvalumab + Tremelimumab | Experimental | Durvalumab 1500 mg IV 60 min Day 1 every 4 weeks Tremelimumab 75 mg IV 60 min Day 1, cycles 1-4 Receives: Drug: Durvalumab; Drug: Tremelimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate Measured by RECIST Version 1.1
Objective response rate is defined as the proportion of response evaluable patients who had complete response (CR) or partial response (PR) as their best response as assessed by RECIST version 1.1 criteria (i.e. a 30% decrease in the sum of the longest diameters of the target lesions maintained for at least 4 weeks (CR), or complete disappearance of disease and cancer related symptoms, also maintained for at least 4 weeks (CR)).
Measured: 48 months
Secondary outcomes (2)
Time to Progression Based on Kaplan-Meier Method
defined as time from the date of randomization to the date of progression
Measured: 48 months
Progression Free Survival Based on Kaplan-Meier Method
defined as time from the date of randomization to the date of progression or death
Measured: 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2016 (estimated)
- Study start14 Dec 2016
- Primary completion20 Jun 2021
- Study completion29 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Rare TumoursStudies of the same condition, open and under way.
- More trials run by Canadian Cancer Trials GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- Canadian Cancer Trials Group
- Sponsor type
- Research network
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Abha Gupta, Study chair, Hospital for Sick Children, Toronto ON Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02879162
- Sponsor's protocol ID
- I228
- Status last verified
- Jan 2025
- First submitted
- 22 Aug 2016
- Last updated
- 7 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gupta AA, Tinker A, Jonker D, Jamal R, Hirte H, Winquist EW, Chu Q, Kollmannsberger C, Wong R, Alcindor T, Nielsen TO, Tsao M, Cottrell TR, Provencher D, Hilton J, Krzyzanowska MK, Elser C, Hotte S, Sederias J, Zhang S, Tu W, Dancey J. Durvalumab and tremelimumab in patients with advanced rare cancer: a multi-centre, non-blinded, open-label phase II basket trial. EClinicalMedicine. 2024 Dec 10;79:102991. doi: 10.1016/j.eclinm.2024.102991. eCollection 2025 Jan.
PubMed 39737219
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Durvalumab and Tremelimumab in Patients With Advanced Rare Tumours
- ClinicalTrials.gov ID
- NCT02879162
- Acronym / sponsor ID
- I228
- Conditions
- Advanced Rare Tumours
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 140 participants (actual)
- Lead sponsor
- Canadian Cancer Trials GroupResearch network
- Collaborators
- AstraZeneca
- Study start
- 14 Dec 2016 (actual)
- Primary completion
- 20 Jun 2021 (actual)
- Study completion
- 29 Jan 2025 (actual)
- First posted
- 25 Aug 2016 (estimated)
- Results
- Posted 17 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The standard or usual treatment for this disease may be chemotherapy or other types of treatment to slow the spread of the disease and relieve some symptoms of this cancer.
Detailed description
Durvalumab is a new type of drug for many types of cancer. Laboratory tests show that it works by allowing the immune system to detect cancer and stimulate the immune response. This may help to slow down the growth of cancer or may cause cancer cells to die. Durvalumab has been shown to shrink tumours in animals and has been studied in 5000 people and seems promising but it is not clear if it can offer better results than standard treatment alone.
Tremelimumab is a new type of drug for various types of cancers. It works in a similar way to durvalumab and may improve the effect of durvalumab. This may also help slow the growth of the cancer cells or may cause cancer cells to die. Tremelimumab has been shown to shrink tumours in animals and has been studied in 1500 people and seems promising but it is not clear if it can offer better results than standard treatment alone when used with durvalumab
Combinations of durvalumab and tremelimumab have also been studied and when combined have been shown to increase tumour shrinkage in animals compared to either drug alone. While the combination has been studied in 250 people, it is not clear if it can offer better results than standard treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Durvalumab + Tremelimumab | Experimental | Drug: Durvalumab, Drug: TremelimumabDurvalumab 1500 mg IV 60 min Day 1 every 4 weeks Tremelimumab 75 mg IV 60 min Day 1, cycles 1-4 |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (36 listed)
- Patients must have histologically and/or cytologically confirmed cancer that is advanced / metastatic / recurrent or unresectable and for which no curative therapy exists as follows:
- All patients must have a tumour tissue from their primary or metastatic tumour available
- Presence of clinically and/or radiologically documented disease. All radiology studies must be performed within 28 days prior to registration (within 35 days if negative).
- All patients must have at least one measurable lesion as defined by RECIST 1.1 that has not been the site of the protocol mandated biopsy. The criteria for defining measurable disease are as follows:
- CT scan (with slice thickness of 5 mm) ≥ 10 mm --> longest diameter Lymph nodes by CT scan ≥ 15 mm --> measured in short axis
Key exclusion criteria (17 listed)
- Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other cancers curatively treated with no evidence of disease for ≥ 5 years.
- Active or prior documented autoimmune or inflammatory disorders including inflammatory bowel disease (e.g. colitis or Crohn's disease), diverticulitis with the exception of diverticulosis, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), rheumatoid arthritis, hypophysitis, uveitis, etc., within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
- History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of registration.
- Live attenuated vaccination administered within 30 days prior to registration.
- History of hypersensitivity to durvalumab or tremelimumab or any excipient. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Durvalumab | Drug | Durvalumab + Tremelimumab |
| Tremelimumab | Drug | Durvalumab + Tremelimumab |
Primary outcome
Objective Response Rate Measured by RECIST Version 1.1
Time frame: 48 months
Objective response rate is defined as the proportion of response evaluable patients who had complete response (CR) or partial response (PR) as their best response as assessed by RECIST version 1.1 criteria (i.e. a 30% decrease in the sum of the longest diameters of the target lesions maintained for at least 4 weeks (CR), or complete disappearance of disease and cancer related symptoms, also maintained for at least 4 weeks (CR)).
2 secondary outcomes
Time to Progression Based on Kaplan-Meier Method
Time frame: 48 months
Progression Free Survival Based on Kaplan-Meier Method
Time frame: 48 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 39737219Gupta AA, Tinker A, Jonker D, Jamal R, Hirte H, Winquist EW, Chu Q, Kollmannsberger C, Wong R, Alcindor T, Nielsen TO, Tsao M, Cottrell TR, Provencher D, Hilton J, Krzyzanowska MK, Elser C, Hotte S, Sederias J, Zhang S, Tu W, Dancey J. Durvalumab and tremelimumab in patients with advanced rare cancer: a multi-centre, non-blinded, open-label phase II basket trial. EClinicalMedicine. 2024 Dec 10;79:102991. doi: 10.1016/j.eclinm.2024.102991. eCollection 2025 Jan.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Abha Gupta study chair
Hospital for Sick Children, Toronto ON Canada
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Durvalumab and Tremelimumab in people with Advanced Rare Tumours, run by Canadian Cancer Trials Group at 13 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 36 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate Measured by RECIST Version 1.1 (time frame: 48 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02879162, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2025.